Since electrospray ionization (ESI) technology was invented by John Fenn in 1984, the electrospray ion source has become the most commonly used ion source in the mass spectrometry field due to characteristics of the ESI such as low ionization energy, easy generation of multiple-charged ions, and easy integration with a liquid chromatograph. It is an important topic in the field on how to improve sensitivity of an electrospray ion source region.
The current limiting factors to sensitivity of electrospray mass spectrometry are mainly from the following aspects. 1. The quantity of generated ions is small. The ion generation process involves forming, evaporation, and Coulomb explosion of spray droplets. In the process, more charges on droplets can be obtained by adjusting electrochemical parameters, surface tension, droplet radius and the like. However, the most important limiting factor in the process is whether droplet desolvation can be thoroughly performed to release gaseous ions. 2. A huge ion loss happens in ions' transmission. Currently, almost all the commercial instruments carry out electrospray under the atmospheric pressure or under a pressure close to the atmospheric pressure, whereas a mass analyzer needs to work under a higher vacuum, so a series of vacuum interfaces and ion guide devices are required to enable ions generated by electrospray to get into the analyzer. As an atmospheric pressure vacuum interface (usually a capillary or a sampling cone with a diameter less than 1 mm) must be kept small to maintain the vacuum in the next stage, over 90% of the ions are lost on the vacuum interface. 3. Severe noise interference often occurs. The noise in the electrospray source is complex, which include matrix effects resulting from competition of charges by impurities like salt and sugar in a real sample, and neutral molecule noise caused by solvent molecules or clusters that are not fully removed or background gas impurities and the like. The neutral molecule noise greatly degrades the sensitivity of a mass spectrometer.
To solve the problems that the quantity of generated ions is small and the desolvation is insufficient, a common method is to introduce a desolvation gas with a high flow rate and high temperature to facilitate the droplets' desolvation process, as shown in U.S. Pat. Nos. 6,759,650 and 8,039,795. However, the desolvation gas with a high flow rate leads to high cost, and the high temperature gas may result in evaporation and even boiling of some volatile solvents, or result in thermal dissociation of certain analytes.
To solve the problem of ion loss at the vacuum interface, the electrospray can be run in very low liquid flow rate so called microspray or nanospray, in which the ESI emitter with a small diameter is employed to reduce the spray volume. As a result, the proportion of ions passing through the interface is increased. The capillary or sampling cone with larger diameter is also feasible, along with higher requirement to the pumping capability in the next vacuum stage. U.S. Pat. No. 6,803,565 discloses a method in which the multi-emitter nanospray coupled with multi-capillary interface, and the method is actually a combination of the above two methods. A more effective method is to perform electrospray directly under a low gas pressure. U.S. Pat. Nos. 5,838,002, 6,068,749, and 7,671,344 disclose a device and a method for performing electrospray under a low gas pressure. Particularly in U.S. Pat. No. 7,671,344, an ion guide device “ion funnel” with a large ion acceptance area is employed to enable most of the ions can be transported and focused into the next vacuum stage. However, this method cannot reduce the coming along noise. Although the “ion funnel” improves the transmission efficiency of ions, it also brings more noises. Moreover, as collisions between droplets and gas molecules are reduced under the low pressure, the insufficiency of the desolvation process gets more severe. Fewer ions which are released from the droplets and more noise from those undesolved droplets give a much lower signal to noise ratio in mass spectrum.
To reduce the coming noise from an electrospray ion source, U.S. Pat. No. 6,730,904 and No. US2011/0049357 disclose two ion guide devices to guide ions in so called off-axis manner. Through such kind of devices, ions are deflected in an electric field, and neutral molecules are pumped away by a rotary pump along a straight path, to implement off-axis transportation of the ions and reduce the noise caused by the neutral molecules. In addition to the complex structures themselves, such devices currently only have been coupled with an atmospheric pressure ion source instead of a low pressure electrospray interface. Therefore, the huge ion loss on the vacuum interface still exists on those devices. The possible reason for that is the typical working pressure of those ion guide devices is below 3 torr or even lower if with reasonable voltage application under disclosed geometry size, whereas the typical pressure for stable and sensitive electrospray is above 10 torr, from the experience of the inventor.
To sum up, there is in need of a method to solve the factors that limit the sensitivity of electrospray, thereby achieving a higher sensitivity of the mass spectrometer.